Topoisomerase II drives DNA transport by hydrolyzing one ATP

DNA topoisomerase II is a homodimeric molecular machine that couples ATP usage to the transport of one DNA segment through a transient break in another segment. In the presence of a non-hydrolyzable ATP analog, the enzyme is known to promote a single turnover of DNA transport. Current models for the...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 96; no. 24; pp. 13685 - 13690
Main Authors Baird, C.L, Harkins, T.T, Morris, S.K, Lindsley, J.E
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 23.11.1999
National Acad Sciences
National Academy of Sciences
Subjects
Adenosine triphosphatases
adenosine triphosphate
Adenosine Triphosphate - metabolism
Biochemistry
Biological Sciences
Biological Transport
Catenanes
Deoxyribonucleic acid
DNA
DNA - metabolism
dna modification
DNA Topoisomerases, Type II - metabolism
enzyme activity
Enzymes
Gels
Hydrolysis
isomerases
Monomers
movement
Plasmids
Saccharomyces cerevisiae
Saccharomyces cerevisiae - enzymology
single turnover decatenation
Vanadates
Yeasts
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Summary:DNA topoisomerase II is a homodimeric molecular machine that couples ATP usage to the transport of one DNA segment through a transient break in another segment. In the presence of a non-hydrolyzable ATP analog, the enzyme is known to promote a single turnover of DNA transport. Current models for the enzyme's mechanism based on this result have hydrolysis of two ATPs as the last step, used only to reset the enzyme for another round of reaction. Using rapid-quench techniques, topoisomerase II recently was shown to hydrolyze its two bound ATPs in a strictly sequential manner. This result is incongruous with the models based on the nonhydrolyzable ATP analog data. Here we present evidence that hydrolysis of one ATP by topoisomerase II precedes, and accelerates, DNA transport. These results indicate that important features of this enzyme's mechanism previously have been overlooked because of the reliance on nonhydrolyzable analogs for studying a single reaction turnover. A model for the mechanism of topoisomerase II is presented to show how hydrolysis of one ATP could drive DNA transport.
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Present address: PE Informatics, 1660 Old Pecos Trail, Suite D, Santa Fe, NM 87505.
Edited by Nicholas R. Cozzarelli, University of California, Berkeley, CA, and approved September 29, 1999
To whom reprint requests should be addressed. E-mail: Janet.Lindsley@hsc.utah.edu.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.24.13685